This is a multidisciplinary collaborative program involving researchers at the Massachusetts Institute of Technology, Harvard Medical School, Massachusetts General Hospital, Brigham and Women's Hospital, and the National Cancer Institute. The hypothesis of this proposal is that optical coherence tomography (OCT), an emerging biomedical diagnostic imaging technology for in situ imaging of tissue microstructure, can be developed and applied for "optical biopsy," the real time, in vivo differentiation and monitoring of early neoplastic changes. This program integrates the development of new technology with its application to fundamental and clinical studies in oncology. The applicants propose to: 1. Develop ultrahigh resolution, spectroscopic, and Doppler OCT technology which extends the current 10-15 (m image resolution to the 1-2 (m level. This is a quantum leap in performance which will significantly improve imaging of architectural morphology and facilitate imaging of cellular features for identifying early neoplastic changes. Spectroscopic and Doppler OCT could enable functional imaging of tissue on a micron scale. 2. Develop delivery instruments for OCT which allow noninvasive or minimally invasive clinical imaging. These include a catheter/endoscope, colposcope, hysteroscope, hand held probe, and needle. 3. Investigate OCT imaging of early neoplastic changes and cancer progression in an animal model to define markers of dysplasia and to develop quantitative assessments of vascular density. A noninvasive, real time technique for quantitating angiogenesis can be a powerful research tool for the development of anti-angiogenesis agents. 4. Investigate OCT imaging in the female reproductive tract including the cervix and endometrium. The cervix is an excellent in vivo model system to establish markers of dysplastic change. Hysteroscopic OCT imaging of the uterus could improve the detection of endometrial dysplasia and cancer. 5. Investigate OCT imaging of dysplasia and leukoplakia of oral mucosa and chemoprevention treatment. Approaches to quantitatively assess response to chemoprevention would be important tools for pharmacological trials. 6. Investigate OCT imaging of the GI tract. Explore the feasibility of OCT for differentiating dysplasia and adenocarcinoma of the esophagus to guide conventional excisional biopsy and reduce false negative rates. Develop OCT as a low cost screening technique for Barrett's esophagus. Taken together, these studies will provide new imaging tools for oncology research and also develop new clinical diagnostic and screening techniques.